Anti-Tac(Fv)-PE38 (LMB-2) to Treat Cutaneous T-Cell Lymphomas

Background: It is estimated that 40-50% of patients with cutaneous T-cell lymphoma (CTCL) have tumors that express cluster of differentiation 25 (CD25) (Tac or IL2Ra). Normal resting T-cells do not express CD25. LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of MAb anti-Tac and truncated Pseudomonas exotoxin. A phase I trial at National Cancer Institute (NCI) found that the maximum tolerated dose (MTD) of LMB-2 was 40 microg/Kg intravenous (IV) given every other day for 3 doses (QOD times 3) with prophylactic IV fluid. The most common adverse events were transient fever, hypoalbuminemia and transaminase elevations. In that trial, two of two patients with cutaneous T-cell lymphoma had clinical benefit (1 partial response (PR), 1 stable disease (SD)). In 1999 another recombinant fusion protein, denileukin diftitox, was approved by the Food and Drug Administration (FDA) for treatment of patients with advanced or recurrent CTCL expressing the high affinity interleukin-2 (IL-2) receptor. This receptor is composed of three subunits: CD25, CD122 and CD132. Because LMB-2 is cytotoxic to cells expressing CD25 without the other IL-2 receptor subunits needed to form the high affinity receptor, CD25+ CTCL patients are good candidates for further testing with LMB-2. Objectives: The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB-2) in patients with Tac-expressing Cutaneous T-cell Lymphoma (CTCL). The primary endpoints of this trial are the response rate and response duration. We will also evaluate LMB-2 immunogenicity, pharmacokinetics, and toxicity, and monitor soluble Tac levels in the serum. These will be evaluated using routine hematologic and clinical evaluation, and when appropriate, by monitoring the phenotype of circulating T-cells or of biopsied tissues using antibodies to CD25. Eligibility: CD25+ CTCL based on immunohistochemistry or flow cytometry of blood. Patients must have measurable stage 1b-IV disease which progressed after greater than or equal 2 prior systemic or topical therapies. Labs required: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5-time upper limit, albumin greater than or equal 3, bilirubin less than or equal to 2.2, creatinine less than or equal to 2.0 (unless creatinine clearance greater than or equal to 50 ml/min), absolute neutrophil count (ANC) greater than or equal to 1000/ul, and platelets greater than or equal to 50,000/ul (ANC and platelets greater than or equal 500 and 10,000 if blood/marrow involvement). Design: Patients receive LMB-2 30 ug/Kg QOD time 3 every 4 weeks in absence of neutralizing antibodies or progressive disease. Dose escalation to 40 ug/Kg QOD times 3 if less than 2/6 dose limiting toxicity (DLT) at 30 ug/Kg times 3. 1st stage is 16 patients, to expand to 25 if greater than 1 of 16 patients respond.